Identification of Let-7f-5p as a novel biomarker of recurrence in non-muscle invasive bladder cancer.
Biomarkers, Tumor
/ genetics
Cell Movement
/ genetics
Cell Proliferation
/ genetics
Female
Gene Expression Regulation, Neoplastic
/ genetics
Humans
Male
MicroRNAs
/ genetics
Middle Aged
Neoplasm Invasiveness
/ genetics
Neoplasm Recurrence, Local
/ genetics
Prognosis
RNA-Binding Proteins
/ genetics
Urinary Bladder Neoplasms
/ genetics
bladder cancer
miR
miRNA
recurrence
urothelial carcinoma
Journal
Cancer biomarkers : section A of Disease markers
ISSN: 1875-8592
Titre abrégé: Cancer Biomark
Pays: Netherlands
ID NLM: 101256509
Informations de publication
Date de publication:
2020
2020
Historique:
pubmed:
6
7
2020
medline:
9
6
2021
entrez:
6
7
2020
Statut:
ppublish
Résumé
Among patients diagnosed with non-muscle invasive bladder cancer (NMIBC), 30% to 70% experience recurrences within 6 to 12 years of diagnosis. The need to screen for these events every 3 to 6 months and ultimately annually by cystoscopy makes bladder cancer one of the most expensive malignancies to manage. The purpose of this study was to identify reproducible prognostic microRNAs in resected non-muscle invasive bladder tumor tissue that are predictive of the recurrent tumor phenotype as potential biomarkers and molecular therapeutic targets. Two independent cohorts of NMIBC patients were analyzed using a biomarker discovery and validation approach, respectively. miRNA Let-7f-5p showed the strongest association with recurrence across both cohorts. Let-7f-5p levels in urine and plasma were both found to be significantly correlated with levels in tumor tissue. We assessed the therapeutic potential of targeting Lin28, a negative regulator of Let-7f-5p, with small-molecule inhibitor C1632. Lin28 inhibition significantly increased levels of Let-7f-5p expression and led to significant inhibition of viability and migration of HTB-2 cells. We have identified Let-7f-5p as a miRNA biomarker of recurrence in NMIBC tumors. We further demonstrate that targeting Lin28, a negative regulator of Let-7f-5p, represents a novel potential therapeutic opportunity in NMIBC.
Sections du résumé
BACKGROUND
BACKGROUND
Among patients diagnosed with non-muscle invasive bladder cancer (NMIBC), 30% to 70% experience recurrences within 6 to 12 years of diagnosis. The need to screen for these events every 3 to 6 months and ultimately annually by cystoscopy makes bladder cancer one of the most expensive malignancies to manage.
OBJECTIVE
OBJECTIVE
The purpose of this study was to identify reproducible prognostic microRNAs in resected non-muscle invasive bladder tumor tissue that are predictive of the recurrent tumor phenotype as potential biomarkers and molecular therapeutic targets.
METHODS
METHODS
Two independent cohorts of NMIBC patients were analyzed using a biomarker discovery and validation approach, respectively.
RESULTS
RESULTS
miRNA Let-7f-5p showed the strongest association with recurrence across both cohorts. Let-7f-5p levels in urine and plasma were both found to be significantly correlated with levels in tumor tissue. We assessed the therapeutic potential of targeting Lin28, a negative regulator of Let-7f-5p, with small-molecule inhibitor C1632. Lin28 inhibition significantly increased levels of Let-7f-5p expression and led to significant inhibition of viability and migration of HTB-2 cells.
CONCLUSIONS
CONCLUSIONS
We have identified Let-7f-5p as a miRNA biomarker of recurrence in NMIBC tumors. We further demonstrate that targeting Lin28, a negative regulator of Let-7f-5p, represents a novel potential therapeutic opportunity in NMIBC.
Identifiants
pubmed: 32623385
pii: CBM191322
doi: 10.3233/CBM-191322
doi:
Substances chimiques
Biomarkers, Tumor
0
Lin28A protein, human
0
MicroRNAs
0
RNA-Binding Proteins
0
mirnlet7 microRNA, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
101-110Subventions
Organisme : NCI NIH HHS
ID : K07 CA102327
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA182659
Pays : United States